NM_000036.3(AMPD1):c.1235C>T (p.Ala412Val) AND Muscle AMP deaminase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 25, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002751285.2

Allele description [Variation Report for NM_000036.3(AMPD1):c.1235C>T (p.Ala412Val)]

NM_000036.3(AMPD1):c.1235C>T (p.Ala412Val)

Gene:

AMPD1:adenosine monophosphate deaminase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p13.2

Genomic location:

Preferred name:

NM_000036.3(AMPD1):c.1235C>T (p.Ala412Val)

HGVS:

NC_000001.11:g.114677504G>A
NG_008012.1:g.23052C>T
NM_000036.3:c.1235C>TMANE SELECT
NM_001172626.2:c.1223C>T
NP_000027.3:p.Ala412Val
NP_001166097.2:p.Ala408Val
NC_000001.10:g.115220125G>A

Protein change:

A408V

Molecular consequence:

NM_000036.3:c.1235C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001172626.2:c.1223C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Muscle AMP deaminase deficiency (MMDD)
Synonyms:: Myoadenylate deaminase deficiency, myopathy due to; Adenosine monophosphate deaminase 1 deficiency; AMP deaminase 1 deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0014220; MedGen: C3714933; Orphanet: 45; OMIM: 615511

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003019936	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 25, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34490048, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003019936

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 25, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical Utility of Rapid Exome Sequencing Combined With Mitochondrial DNA Sequencing in Critically Ill Pediatric Patients With Suspected Genetic Disorders.

Ouyang X, Zhang Y, Zhang L, Luo J, Zhang T, Hu H, Liu L, Zhong L, Zeng S, Xu P, Bai Z, Wong LJ, Wang J, Wang C, Wang B, Zhang VW.

Front Genet. 2021;12:725259. doi: 10.3389/fgene.2021.725259.

PubMed [citation]

PMID:: 34490048
PMCID:: PMC8416976

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003019936.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 445 of the AMPD1 protein (p.Ala445Val). This variant is present in population databases (rs770870863, gnomAD 0.003%). This missense change has been observed in individual(s) with AMPD1-related conditions (PMID: 34490048). ClinVar contains an entry for this variant (Variation ID: 1981141). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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